H.-C. Schuppe

Influence of urogenital infections and inflammation on semen quality and male fertility

BackgroundUrogenital infections and inflammation are a significant etiologic factor in male infertility.MethodsData for this review were acquired by a systematic search of the medical literature. Relevant cross-references were also taken into account.ResultsWe address infectious and inflammatory diseases of different compartments of the male genital tract and discuss their andrological sequelae. Chronic urethritis might be responsible for silent genital tract inflammation with negative impact on semen quality. In chronic pelvic pain syndrome, morphological abnormalities of spermatozoa and seminal plasma alterations are detectable. In the majority of men with epididymitis, a transient impairment of semen quality can be found during the acute infection. However, persistent detrimental effects are not uncommon, even after complete bacteriological cure. The relevance of chronic viral infections as an etiologic factor in male infertility is believed to be underestimated. Data concerning the impact of HIV infection on male fertility are of increasing interest as with the improvement in life expectancy, issues of sexuality and procreation gain importance. Moreover, effects of noninfectious systemic inflammation on the male reproductive tract have to be considered in patients with metabolic syndrome, a disorder of growing relevance worldwide. Finally, microbiological and related diagnostic findings in urine and semen samples are reviewed according to their relevance for male infertility.ConclusionsAvailable data provide sufficient evidence that in men with alterations of the ejaculate, urogenital infections and inflammation have to be considered.

Acute epididymitis in ultrasound: Results of a prospective study with baseline and follow-up investigations in 134 patients

OBJECTIVES To perform a comprehensive follow-up analysis of ultrasonographic scrotal features and associated signs in patients with acute epididymitis. METHODS Between 2007 and 2012, 134 adults (median age 54 years) with acute epididymitis underwent scrotal ultrasonography and palpation at first presentation and after 2 weeks and 3 months. RESULTS At first presentation, 61 patients (45.5%) had hydrocele, 63 (47.0%) concomitant orchitis, and 8 (5.9%) epididymal abscess. Epididymitis was predominantly located in 24 cases (17.9%) in the head, 52 cases (38.8%) in the tail, and 58 cases (43.3%) in both. On the affected side, testicular volume was 16.9 ± 6.8 ml and peak systolic velocity of the testicular artery was 23.7 ± 7.5 cm/s, compared to the healthy side with 12.3 ± 4.4 ml and 9.5 ± 3.6 cm/s respectively (P<0.001). Concomitant orchitis was associated with hydrocele, testicular enlargement and pain (P<0.01). Orchiectomy due to secondary testicular infarction was necessary in four cases, while in all other patients ultrasound parameters normalized. Only 16/90 patients (17.8%) showed a persistent epididymal swelling after 3 months. CONCLUSIONS Common ultrasound features include hydrocele, epididymal enlargement, hyperperfusion, and testicular involvement. Under conservative treatment, ultrasound parameters normalize without evidence of testicular atrophy even in patients with epididymal abscess or concomitant orchitis.

Experimental Escherichia coli epididymitis in rats: assessment of testicular involvement in a long-term follow-up.

The objective of this study was to investigate spermatogenesis and testicular inflammation in a rat model of unilateral Escherichia coli epididymitis in a long‐term follow‐up. Unilateral epididymitis was induced in 30 Sprague‐Dawley rats by injecting E. coli into the right ductus deferens. Oral antimicrobial treatment with sparfloxacin (50 mg kg−1 body weight/7 days) was administered in half of the animals 24 h after infection. Five treated and five untreated rats were killed at 2 weeks, 3 months and 6 months after infection. Spermatogenesis was investigated using a histological semi‐quantitative score. The presence of inflammatory cells (B‐ and T lymphocytes, macrophages and granulocytes) in the testicular tissues was evaluated by immunohistochemistry. The testes were sterile at all times. Over the course of 6 months, spermatogenesis underwent significant incremental impairment on the inoculated side as compared to the contralateral side (P < 0.001). However, overall spermatogenesis scores were not significantly different between treated and untreated animals (P > 0.3 at each time point). Finally, loss of testicular architecture on the inoculated side was not associated with any cellular inflammatory response. Thus, adjuvant therapies need to be studied, and research is necessary on how to prevent deterioration of testicular function in bacterial epididymitis.

Validation of the German version of the ‘Hypogonadism Related Symptom Scale’ (HRS) in andrological patients with infertility, HIV infection and metabolic syndrome

As commonly used self‐reported screening instruments for male hypogonadism demonstrated lack of specificity, a Hypogonadism Related Symptom Scale (HRS) was developed in 2009 as a novel self‐rating screening tool. As the questionnaire has not been validated, the purpose of our study was to perform a validation in patients presenting with different disorders (e.g. infertility, HIV infection or metabolic syndrome) and disease‐related risk to develop hypogonadism. Two hundred and eighteen patients aged 19–71 years (40.1 ± 9.5) who completed the HRS and other common questionnaires [International Index Of Erectile Function (IIEF), National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI), Hospital Anxiety and Depression Scale (HADS), short form (SF)‐12] were included. In all patients, blood levels of total testosterone, luteinizing hormone, follicle‐stimulating hormone, oestradiol and sex hormone‐binding globulin were determined and free testosterone was calculated. Cronbachs α for the scale was 0.896, split‐half 0.871 for the 1st half and 0.807 for the 2nd half. Spearman–Brown coefficient was 0.767, and Guttman split‐half coefficient was 0.759. Consistent correlations were found between HRS and IIEF5 (ρ = 0.57, P < 0.001), and HADS (ρ = −0.6, P < 0.001). In addition, HRS was significantly correlated with total testosterone (ρ = 0.135, P < 0.05), free testosterone (ρ = 0.148, P < 0.05) and oestradiol (ρ = −0.134, P < 0.05). Our validation study confirms the data from the initial development of the HRS questionnaire. Clinicians might have an additional advantage from the HRS when investigating males with suspected hypogonadism.

Orchitis und Infertilität

ZusammenfassungInfektionen und Entzündungen des Genitaltraktes werden zu den häufigsten Ursachen einer eingeschränkten Fertilität beim Mann gezählt, gesicherte epidemiologische Daten stehen allerdings nicht zur Verfügung. Mit Blick auf die Exposition der Keimzellen gegenüber Erregern bzw. Erregerbestandteilen sowie den an Entzündungsprozessen beteiligten Zellen und Mediatoren muss insbesondere bei chronischen Hodenentzündungen mit einer irreversiblen Schädigung der Spermatogenese und einer entsprechenden Verschlechterung der Ejakulatqualität gerechnet werden. Während für die klinisch symptomatischen Orchitiden bzw. Epididymoorchitiden aufgrund systemischer oder lokaler Infektionen entsprechende Folgen bis hin zu Hodenatrophie und vollständigem Verlust der Fertilität bekannt sind, fanden asymptomatisch bzw. subklinisch verlaufende, auch nicht erregerbedingte testikuläre Entzündungsreaktionen diesbezüglich bisher wenig Beachtung. Systematische histopathologische Untersuchungen zeigen jedoch eine hohe Prävalenz asymptomatischer Entzündungsreaktionen in Hodenbiopsien infertiler Männer. Die meist fokalen, überwiegend lymphozytären Infiltrate korrelieren mit dem Schädigungsgrad der Spermatogenese und entsprechenden klinisch-endokrinologischen Parametern der Hodenfunktion. Eine nichtinvasive Diagnostik steht bisher nicht zur Verfügung, so dass chronische, asymptomatische Hodenentzündungen als primäre Ursache oder Kofaktor männlicher Fertilitätsstörungen unterschätzt werden. Abgesehen von einer erregergerechten Antibiotikagabe fehlen Therapieempfehlungen noch weitgehend.AbstractInfections and inflammations of the genital tract are considered the most frequent causes of reduced male fertility, but conclusive epidemiological data are not available. In view of the exposure of germ cells to pathogenic components as well as the cells and mediators involved in the inflammatory processes, irreversible damage to spermatogenesis and corresponding decline of ejaculate quality are to be expected, particularly in cases of chronic orchitis. While the consequences of orchitis and epididymo-orchitis that exhibit clinical symptoms due to systemic or local infections are well known, including testicular atrophy and complete loss of fertility, those cases of inflammatory reactions of the testicles that manifest an asymptomatic or subclinical course, or are not even due to an infection, have received little attention until now. However, systematic histopathological analyses have shown a high prevalence of asymptomatic inflammatory reactions in testicular biopsies from infertile men. The mostly focal lymphocytic infiltrates correlate with the degree of damage to spermatogenesis and corresponding clinical and endocrinological parameters of testicular function. Noninvasive diagnostic techniques are not yet available so that chronic asymptomatic inflammations of the testicles as the primary cause or cofactor of male fertility disorders are underestimated. Except for administration of pathogen-specific antibiotics, treatment recommendations are to a large extent still lacking.

Orchitis and male infertility

ZusammenfassungInfektionen und Entzündungen des Genitaltraktes werden zu den häufigsten Ursachen einer eingeschränkten Fertilität beim Mann gezählt, gesicherte epidemiologische Daten stehen allerdings nicht zur Verfügung. Mit Blick auf die Exposition der Keimzellen gegenüber Erregern bzw. Erregerbestandteilen sowie den an Entzündungsprozessen beteiligten Zellen und Mediatoren muss insbesondere bei chronischen Hodenentzündungen mit einer irreversiblen Schädigung der Spermatogenese und einer entsprechenden Verschlechterung der Ejakulatqualität gerechnet werden. Während für die klinisch symptomatischen Orchitiden bzw. Epididymoorchitiden aufgrund systemischer oder lokaler Infektionen entsprechende Folgen bis hin zu Hodenatrophie und vollständigem Verlust der Fertilität bekannt sind, fanden asymptomatisch bzw. subklinisch verlaufende, auch nicht erregerbedingte testikuläre Entzündungsreaktionen diesbezüglich bisher wenig Beachtung. Systematische histopathologische Untersuchungen zeigen jedoch eine hohe Prävalenz asymptomatischer Entzündungsreaktionen in Hodenbiopsien infertiler Männer. Die meist fokalen, überwiegend lymphozytären Infiltrate korrelieren mit dem Schädigungsgrad der Spermatogenese und entsprechenden klinisch-endokrinologischen Parametern der Hodenfunktion. Eine nichtinvasive Diagnostik steht bisher nicht zur Verfügung, so dass chronische, asymptomatische Hodenentzündungen als primäre Ursache oder Kofaktor männlicher Fertilitätsstörungen unterschätzt werden. Abgesehen von einer erregergerechten Antibiotikagabe fehlen Therapieempfehlungen noch weitgehend.AbstractInfections and inflammations of the genital tract are considered the most frequent causes of reduced male fertility, but conclusive epidemiological data are not available. In view of the exposure of germ cells to pathogenic components as well as the cells and mediators involved in the inflammatory processes, irreversible damage to spermatogenesis and corresponding decline of ejaculate quality are to be expected, particularly in cases of chronic orchitis. While the consequences of orchitis and epididymo-orchitis that exhibit clinical symptoms due to systemic or local infections are well known, including testicular atrophy and complete loss of fertility, those cases of inflammatory reactions of the testicles that manifest an asymptomatic or subclinical course, or are not even due to an infection, have received little attention until now. However, systematic histopathological analyses have shown a high prevalence of asymptomatic inflammatory reactions in testicular biopsies from infertile men. The mostly focal lymphocytic infiltrates correlate with the degree of damage to spermatogenesis and corresponding clinical and endocrinological parameters of testicular function. Noninvasive diagnostic techniques are not yet available so that chronic asymptomatic inflammations of the testicles as the primary cause or cofactor of male fertility disorders are underestimated. Except for administration of pathogen-specific antibiotics, treatment recommendations are to a large extent still lacking.

[News from andrology. Infertility, erectile dysfunction, and hypogonadism].

ZusammenfassungDer Beitrag bespricht neue Aspekte der Andrologie für die Schwerpunkte Infertilität, erektile Dysfunktion (ED) und Hypogonadismus. Themen wie Prostatitis und Chlamydiennachweis, idiopathische Infertilität und PDE5-Inhibitoren, ED nach Greenlight-Lasertherapie werden erörtert.AbstractThis contribution discusses new aspects in andrology focusing on infertility, erectile dysfunction (ED), and hypogonadism. Topics such as prostatitis and detection of Chlamydia, idiopathic infertility and PDE5 inhibitors, and ED after GreenLight laser treatment are addressed.This contribution discusses new aspects in andrology focusing on infertility, erectile dysfunction (ED), and hypogonadism. Topics such as prostatitis and detection of Chlamydia, idiopathic infertility and PDE5 inhibitors, and ED after GreenLight laser treatment are addressed.

Neues in der Andrologie

ZusammenfassungDer Beitrag bespricht neue Aspekte der Andrologie für die Schwerpunkte Infertilität, erektile Dysfunktion (ED) und Hypogonadismus. Themen wie Prostatitis und Chlamydiennachweis, idiopathische Infertilität und PDE5-Inhibitoren, ED nach Greenlight-Lasertherapie werden erörtert.AbstractThis contribution discusses new aspects in andrology focusing on infertility, erectile dysfunction (ED), and hypogonadism. Topics such as prostatitis and detection of Chlamydia, idiopathic infertility and PDE5 inhibitors, and ED after GreenLight laser treatment are addressed.This contribution discusses new aspects in andrology focusing on infertility, erectile dysfunction (ED), and hypogonadism. Topics such as prostatitis and detection of Chlamydia, idiopathic infertility and PDE5 inhibitors, and ED after GreenLight laser treatment are addressed.

Orchitis und Infertilität@@@Orchitis and male infertility

ZusammenfassungInfektionen und Entzündungen des Genitaltraktes werden zu den häufigsten Ursachen einer eingeschränkten Fertilität beim Mann gezählt, gesicherte epidemiologische Daten stehen allerdings nicht zur Verfügung. Mit Blick auf die Exposition der Keimzellen gegenüber Erregern bzw. Erregerbestandteilen sowie den an Entzündungsprozessen beteiligten Zellen und Mediatoren muss insbesondere bei chronischen Hodenentzündungen mit einer irreversiblen Schädigung der Spermatogenese und einer entsprechenden Verschlechterung der Ejakulatqualität gerechnet werden. Während für die klinisch symptomatischen Orchitiden bzw. Epididymoorchitiden aufgrund systemischer oder lokaler Infektionen entsprechende Folgen bis hin zu Hodenatrophie und vollständigem Verlust der Fertilität bekannt sind, fanden asymptomatisch bzw. subklinisch verlaufende, auch nicht erregerbedingte testikuläre Entzündungsreaktionen diesbezüglich bisher wenig Beachtung. Systematische histopathologische Untersuchungen zeigen jedoch eine hohe Prävalenz asymptomatischer Entzündungsreaktionen in Hodenbiopsien infertiler Männer. Die meist fokalen, überwiegend lymphozytären Infiltrate korrelieren mit dem Schädigungsgrad der Spermatogenese und entsprechenden klinisch-endokrinologischen Parametern der Hodenfunktion. Eine nichtinvasive Diagnostik steht bisher nicht zur Verfügung, so dass chronische, asymptomatische Hodenentzündungen als primäre Ursache oder Kofaktor männlicher Fertilitätsstörungen unterschätzt werden. Abgesehen von einer erregergerechten Antibiotikagabe fehlen Therapieempfehlungen noch weitgehend.AbstractInfections and inflammations of the genital tract are considered the most frequent causes of reduced male fertility, but conclusive epidemiological data are not available. In view of the exposure of germ cells to pathogenic components as well as the cells and mediators involved in the inflammatory processes, irreversible damage to spermatogenesis and corresponding decline of ejaculate quality are to be expected, particularly in cases of chronic orchitis. While the consequences of orchitis and epididymo-orchitis that exhibit clinical symptoms due to systemic or local infections are well known, including testicular atrophy and complete loss of fertility, those cases of inflammatory reactions of the testicles that manifest an asymptomatic or subclinical course, or are not even due to an infection, have received little attention until now. However, systematic histopathological analyses have shown a high prevalence of asymptomatic inflammatory reactions in testicular biopsies from infertile men. The mostly focal lymphocytic infiltrates correlate with the degree of damage to spermatogenesis and corresponding clinical and endocrinological parameters of testicular function. Noninvasive diagnostic techniques are not yet available so that chronic asymptomatic inflammations of the testicles as the primary cause or cofactor of male fertility disorders are underestimated. Except for administration of pathogen-specific antibiotics, treatment recommendations are to a large extent still lacking.

12th Andrology Symposium/5th Symposium of the Hessian Center for Reproductive Medicine and EAA Center Giessen.

Ten years after the 3rd Giessen Andrology Symposium in 1996, which was focussed on ‘Urogenital Infections and Fertility’, the 12th Andrological Symposium re-evaluated the role of urogenital infections and inflammatory conditions from an andrological point of view. As 10 years ago, a correct diagnosis of male adnexitis has to consider the major source of inflammatory products within the ejaculate and expressed prostatic secretions. Therefore, chronic prostatitis has to be ruled out in every case of male accessory gland infection. Nevertheless, reliable studies on prostatic function are lacking, and during the symposium data concerning altered secretory parameters of the prostate gland and their relevance for male infertility were discussed controversially. Seminal parameters under debate for establishing the diagnosis ‘male urogenital inflammation’ include increased numbers of peroxidasepositive cells, elastase, cytokines, and perhaps the significance of increased titres of sperm auto-antibodies, and elevated levels of reactive oxygen species. The central problem is to prove impaired fertility in cases where one of these altered conditions is observed. Unfortunately, there are no sufficiently controlled clinical studies that could have demonstrated improved sperm quality or increased pregnancy rates after eradication of such factors. The same applies to the efficacy of antibiotic therapy where pertinent data are also missing to show improved male fertility after elimination of bacteria from urogenital secretions. On the other hand, the species and the number of microorganisms in the ejaculate appear to play an important role for the outcome of assisted reproductive techniques. In 1996, one consensus of the conference was the lack of standard procedures to identify the different inflammatory entities of male accessory gland infections. Now there is consensus that NIH suggestions for the definition of the prostatitis syndrome should be accepted by all specialists involved in the field of andrology. The WHO has suggested that two of the following criteria have to be fulfilled to diagnose male accessory gland infection in men with oligo-, asthenoand/or teratozoospermia: (1) history or physical signs of urinary tract infection, epididymitis, or abnormal rectal examination; (2) abnormal urine after prostatic massage (describing the 4-glass test); (3) elevated numbers of peroxidase positive WBCs, high numbers of bacteria in semen, Chlamydia trachomatis findings, and/or abnormal biochemistry or elevated inflammatory markers in the seminal fluid. Analysis of prostatic fluid is not recommended. In the light of the symposium held in Giessen, it is our consensus that this suggested classification does not sufficiently allow to distinguish between inflammation of different compartments of the male urogenital tract, e.g. prostatitis versus epididymitis/epididymo-orchitis or inflammatory alterations of the urethral compartment. Although the majority of urogenital inflammatory disorders are of infectious origin, also non-infectious causes of inflammation have to be considered. In conclusion, the currently most popular definition and diagnostic criteria for ‘male accessory gland infection’ are not appropriate as a rational tool for the differential diagnosis of inflammatory conditions of the male urogenital tract.